Widely Used Drugs Tied to Greater Dementia Risk for Seniors

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People over age 65 who frequently take over-the-counter sleep
aids and certain other commonly used drugs may be increasing
their risk of dementia, new findings show.

In the study, the researchers looked at drugs that have
"anticholinergic effects," meaning they block a
neurotransmittercalled acetylcholine. Many drugs fall into this
class, including
tricyclic antidepressants such as doxepin, antihistamines
like Chlor-Trimeton (chlorpheniramine) and drugs like Detrol
(oxybutinin) used to treat overactive bladder.

"We have known for some time that even single doses of these
medications can cause impairment in cognition, slower reaction
time, [and] reduced attention and ability to concentrate," said
Shelly Gray, the study's first author and a pharmacy professor at
the University of Washington in Seattle. Originally, "the
thinking was that these
cognitive effects were reversible when you stopped taking the
medication."

But Gray's study found a link between heavier use of these
medications and
dementia, "which is a nonreversible, severe form of cognitive
impairment," she said.

Studies have shown as much as 37 percent of people over age 65
use anticholinergic medications, Gray and her team noted in their
report, published today (Jan. 26) in the journal JAMA Internal
Medicine. Some previous studies had linked the drugs to permanent
cognitive changes, including dementia, but all of these studies
had "important limitations," the authors wrote. [ 6
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For example, some studies failed to take into account that some
anticholinergic drugs are used to treat depression and insomnia,
which can be early warning signs of dementia. "If you don't
account for that, it looks like the
medication is causing the dementia, while it's really those
symptoms that are causing that anticholinergic use," Gray said.

In the new study, Gray and her colleagues looked at data from the
prospective Adult Changes in Thought study, which includes
patients from Group Health, a health-care delivery system in
Seattle. The researchers identified 3,434 people who were ages 65
and older and were free from dementia at the start of the study.

During follow-up, which lasted an average of about seven years,
797 study participants (23.2 percent) were diagnosed with
dementia, and about 80 percent of these individuals had
Alzheimer's disease. The researchers found that the higher a
patient's cumulative dose of anticholinergic medication over the
10 years before entering the study, the greater his or her risk
of dementia.

A secondary analysis by the researchers showed that it didn't
seem to matter when the patient had used the medications during
the previous 10 years; it just mattered how much the individual
had used in total.

The researchers also analyzed the data after omitting the
patients' prescription information for the first year, or two
years, before they were diagnosed with dementia. This was done to
address concerns that the drugs might be used to treat what were
actually the early
signs of dementia. The results remained the same after the
omissions, however.

Based on the findings, people who took 10 milligrams of doxepin
daily for a total of three years would be at increased risk of
dementia, the researchers said. The same was true of people who
take 4 milligrams of chlorpheniramine daily, or 5
milligrams of oxybutinin daily.

"Some anticholinergic medications are important for older adults,
so I would urge them not to stop taking any medications that are
anticholinergic until they speak to their health care provider,"
Gray told Live Science, referring to prescribed medications. She
also suggested that older people give their doctor a list of all
the over-the-counter medications they use, "so that the health
care provider can look for opportunities to reduce unnecessary
anticholinergic medication use."

Some study participants have consented to postmortem brain
autopsies, Gray noted. "We will be looking at whether those with
high anticholinergic use also have brain
pathology consistent with dementia to try and understand the
underlying mechanisms," she said.

Noll Campbell and Malaz Boustani, of the Regenstrief Institute in
Indianapolis and the Indiana University Center for Aging Research
wrote a commentary accompanying the new study, where they argued
that the adverse effects of these medications may be reversible,
especially in the early stages.

In a statement, Campbell said the study's findings may be a
result of the researchers using dementia as an outcome, instead
of the less condition called severe mild cognitive impairment,
which may be reversible in some older adults. "Our previous
studies have shown a stronger association of these harmful
medications with the diagnosis of mild cognitive impairment than
with dementia," he said.